Hif-1Α Mediated Osteoclastogenesis Accelerates Orthodontic Tooth Movement Via TFRC

This study aimed to elucidate the role of the HIF-1α-TFRC axis in regulating hypoxia-driven osteoclastogenesis during orthodontic tooth movement (OTM) and explore its potential for accelerating orthodontic treatment in adults. HIF-1α knockout mice with Cathepsin K (CTSK) Cre were used to assess osteoclast activity and OTM. In vitro, RAW264.7 cells were treated with CoCl2 to mimic hypoxia and evaluate TFRC's role in osteoclast differentiation. RNA sequencing identified HIF-1α targets in osteoclasts. Desferrioxamine (DFO), a hypoxia mimetic, was administered to mice to validate HIF-1α-TFRC effects on OTM. Osteoclastogenesis and OTM distance were analyzed via histology, TRAP staining, and micro-CT. HIF-1α expression and osteoclast activity increased during OTM in wild-type mice, while HIF-1α knockout reduced osteoclastogenesis and OTM distance. RNA sequencing revealed TFRC as a key HIF-1α target, with CoCl2-treated RAW264.7 cells showing upregulated TFRC and enhanced osteoclast differentiation. DFO treatment in mice accelerated OTM by 30%, increased osteoclast numbers by 50%, and elevated TFRC expression, confirming HIF-1α-TFRC's regulatory role in bone remodeling. The HIF-1α-TFRC axis critically regulates hypoxia-induced osteoclastogenesis and OTM efficiency. Targeting this pathway, such as via DFO-mediated hypoxia mimicry, may offer a therapeutic strategy to accelerate orthodontic treatment in adults by enhancing bone remodeling.